Abstract：
Orexin A and B (OXA and OXB) and their receptors are expressed in the majority of retinal neurons in humans, rats, and mice. Orexins modulate signal transmission between the different layers of the retina. The suprachiasmatic nucleus (SCN) and the retina are central and peripheral components of the body\'s biological clocks; respectively. The SCN receives photic information from the retina through the retinohypothalamic tract (RHT) to synchronize bodily functions with environmental changes. In present study, we aimed to investigate the impact of inhibiting retinal orexin receptors on the expression of retinal Bmal1 and c-fos, as well as hypothalamic c-fos, Bmal1, Vip, and PACAP at four different time-points (Zeitgeber time; ZT 3, 6, 11, and ZT-0). The intravitreal injection (IVI) of OX1R antagonist (SB-334867) and OX2R antagonist (JNJ-10397049) significantly up-regulated c-fos expression in the retina. Additionally, compared to the control group, the combined injection of SB-334867 and JNJ-10397049 showed a greater increase in retinal expression of this gene. Moreover, the expression of hypothalamic Vip and PACAP was significantly up-regulated in both the SB-334867 and JNJ-10397049 groups. In contrast, the expression of Bmal1 was down-regulated. Furthermore, the expression of hypothalamic c-fos was down-regulated in all groups treated with SB-334867 and JNJ-10397049. Additionally, the study demonstrated that blocking these receptors in the retina resulted in alterations in circadian rhythm parameters such as mesor, amplitude, and acrophase. Finally, it affected the phase of gene expression rhythms in both the retina and hypothalamus, as identified through cosinor analysis and the zero-amplitude test. This study represents the initial exploration of how retinal orexin receptors influence expression of rhythmic genes in the retina and hypothalamus. These findings could provide new insights into how the retina regulates the circadian rhythm in both regions and illuminate the role of the orexinergic system expression within the retina.
摘要：
OrexinA和B（OXA和OXB）及其受体在人类大多数视网膜神经元中表达，老鼠,和老鼠。食欲素调节视网膜不同层之间的信号传输。视交叉上核（SCN）和视网膜分别是人体生物钟的中枢和外周成分。SCN通过视网膜下丘脑束（RHT）从视网膜接收光信息，以使身体功能与环境变化同步。在目前的研究中,我们旨在研究抑制视网膜食欲素受体对视网膜Bmal1和c-fos表达的影响，以及下丘脑c-fos，Bmal1,Vip,和PACAP在四个不同的时间点（Zeitgeber时间；ZT3、6、11和ZT-0）。OX1R拮抗剂(SB-334867)和OX2R拮抗剂(JNJ-10397049)的玻璃体内注射(IVI)显著上调视网膜中的c-fos表达。此外,与对照组相比，SB-334867和JNJ-10397049的联合注射显示该基因的视网膜表达增加。此外，SB-334867和JNJ-10397049组均显著上调下丘脑Vip和PACAP的表达.相比之下,Bmal1的表达下调。此外，在SB-334867和JNJ-10397049治疗组,下丘脑c-fos的表达均下调.最后,该研究表明，阻断视网膜中的这些受体会导致昼夜节律参数的改变，如mesor，振幅,和顶相。此外,它影响了视网膜和下丘脑基因表达节律的相位，通过余弦分析和零振幅测试确定。这项研究代表了对视网膜食欲素受体如何影响视网膜和下丘脑中节律基因表达的初步探索。这些发现可以为视网膜如何调节这两个区域的昼夜节律提供新的见解，并阐明视网膜内食欲能系统表达的作用。
